7-2513247-AGATGGATGGATGGATG-AGATGGATGGATG

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001166355.2(LFNG):c.163_166delGATG(p.Asp55SerfsTer141) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 1,581,536 control chromosomes in the GnomAD database, including 3,124 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.074 ( 951 hom., cov: 0)

Exomes 𝑓: 0.024 ( 2173 hom. )

Consequence

LFNG
NM_001166355.2 frameshift

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.823

Publications

13 publications found

Variant links:

Genes affected

LFNG (HGNC:6560): (LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase) This gene is a member of the glycosyltransferase 31 gene family. Members of this gene family, which also includes the MFNG (GeneID: 4242) and RFNG (GeneID: 5986) genes, encode evolutionarily conserved glycosyltransferases that act in the Notch signaling pathway to define boundaries during embryonic development. While their genomic structure is distinct from other glycosyltransferases, these proteins have a fucose-specific beta-1,3-N-acetylglucosaminyltransferase activity that leads to elongation of O-linked fucose residues on Notch, which alters Notch signaling. The protein encoded by this gene is predicted to be a single-pass type II Golgi membrane protein but it may also be secreted and proteolytically processed like the related proteins in mouse and Drosophila (PMID: 9187150). Mutations in this gene have been associated with autosomal recessive spondylocostal dysostosis 3. [provided by RefSeq, May 2018]

LFNG Gene-Disease associations (from GenCC):

spondylocostal dysostosis 3, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
autosomal recessive spondylocostal dysostosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LFNG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 7-2513247-AGATG-A is Benign according to our data. Variant chr7-2513247-AGATG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 403030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LFNG	NM_001166355.2 link	c.163_166delGATG	p.Asp55SerfsTer141	frameshift_variant	Exon 2 of 9		NP_001159827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000402506.5 link	c.163_166delGATG	p.Asp55SerfsTer141	frameshift_variant	Exon 2 of 9	2		ENSP00000385764.1

Frequencies

GnomAD3 genomes

AF:

0.0744

AC:

11234

AN:

151062

Hom.:

952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0680

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.00287

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.00594

Gnomad OTH

AF:

0.0651

GnomAD4 exome

AF:

0.0238

AC:

34042

AN:

1430358

Hom.:

2173

AF XY:

0.0250

AC XY:

17825

AN XY:

711870

show subpopulations

African (AFR)

AF:

0.214

AC:

6883

AN:

32096

American (AMR)

AF:

0.0720

AC:

3188

AN:

44258

Ashkenazi Jewish (ASJ)

AF:

0.0183

AC:

469

AN:

25606

East Asian (EAS)

AF:

0.193

AC:

7403

AN:

38410

South Asian (SAS)

AF:

0.0964

AC:

8162

AN:

84672

European-Finnish (FIN)

AF:

0.00439

AC:

230

AN:

52400

Middle Eastern (MID)

AF:

0.0458

AC:

259

AN:

5660

European-Non Finnish (NFE)

AF:

0.00472

AC:

5134

AN:

1088214

Other (OTH)

AF:

0.0392

AC:

2314

AN:

59042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1545

3089

4634

6178

7723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

574

1148

1722

2296

2870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0744

AC:

11242

AN:

151178

Hom.:

951

Cov.:

AF XY:

0.0758

AC XY:

5595

AN XY:

73802

show subpopulations

African (AFR)

AF:

0.196

AC:

8066

AN:

41058

American (AMR)

AF:

0.0682

AC:

1039

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.0170

AC:

AN:

3462

East Asian (EAS)

AF:

0.201

AC:

1023

AN:

5084

South Asian (SAS)

AF:

0.101

AC:

483

AN:

4790

European-Finnish (FIN)

AF:

0.00287

AC:

AN:

10456

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00593

AC:

402

AN:

67798

Other (OTH)

AF:

0.0644

AC:

135

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

469

937

1406

1874

2343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0135

Hom.:

525

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Not reported. No information available. Gene not associated to pt disease. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 07, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.82

Mutation Taster

=168/32

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over